Inhibition of Ehrlich ascites tumor in vivo by PAF-antagonists.
Several lines of evidence support that PAF modulates the inflammatory and immune responses, and that tumors may inhibit both these processes. In the present study we analysed the effect of PAF antagonists on the growth of Ehrlich Ascites Tumor (EAT) in vivo. Mice were inoculated intraperitoneally with 1 x 10(3) EAT cells and the tumor growth evaluated by counting the number of peritoneal cells, 1,6 and 10 days after tumor implantation. BN 52021 was administered intraperitoneally, intravenously or subcutaneously once or twice a day, at 1.0, 2.5, 5.0 and 20.0 mg/kg. Control animals received 0.1 ml of the vehicle in the same schedule. It was found that i.p. and i.v. administration of BN 52021 (5 mg/kg, twice a day) significantly inhibited EAT growth (80.8% and 56.0% respectively). Other routes and doses were less effective. Another PAF antagonist, SRI 63441 (5 mg/kg, i.p., twice a day) also inhibited EAT growth (80.4%). The BN 52021 added to EAT cells in culture, at concentration of 10(-3) and 10(-4) M, did not affect the viability and proliferation of tumors cells. In an attempt to understand the mechanism of this inhibition, we analyzed the peritoneal macrophages for spreading ability and H2O2 release. It was found that 24 h after tumor implantation there was an increase in the spreading ability of peritoneal macrophages (75%) and that, as the tumor grew, the spreading index fell to control levels ( less than 10%). (5 mg/kg/twice a day) the spreading remained elevated (50-60%) at all the times examined. Release of H2O2, measured by horseradish peroxidase-phenol red oxidation, was below detectable levels throughout tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Fecchio
D
D
Departamento de Imunologia, Universidade de São Paulo, Brazil.
Russo
M
M
Sirois
P
P
Braquet
P
P
Jancar
S
S
D000818:Animals; D000970:Antineoplastic Agents; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes; D046934:Ginkgolides; D006861:Hydrogen Peroxide / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011806:Quinolinium Compounds / Q000494:pharmacology
D000970:Antineoplastic Agents; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C050531:SRI 63-441; D006861:Hydrogen Peroxide; C045856:ginkgolide B